Tissue engineering scaffolds may be used to create inductive microenvironments capable of promoting specific cellular processes or for use as therapeutic devices based on cell replacement. Microporous PLG scaffolds significantly improve the efficacy of pancreatic islet grafts in a murine model of type I diabetes mellitus. The scaffold provides a framework upon which cells may secrete ECM molecules and self-organize. This proposal employs a scaffold to present extracellular matrix components and deliver plasmid DNA encoding betacellulin, a growth factor known to be present in the endogenous islet microenvironment. The aims proposed herein will test the role of these factors in enhancing islet survival and function through a series of experiments that assess the role of these factors in isolation and in combination. These studies will further our understanding of the underlying biology of islet cells and identify design parameters for tissue engineering scaffolds used to improve islet graft survival and function for the treatment of type I diabetes. [unreadable] [unreadable] [unreadable]